Showing papers by "Andrea De Gaetano published in 2020"

Insulin sensitivity depends on the route of glucose administration.

Abstract: The small intestine plays an important role in hepatic and whole-body insulin sensitivity, as shown by bariatric surgery. Our goal was to study whether routes and dose of glucose administration have an acute impact on insulin sensitivity. The primary endpoint of this proof-of-concept study was the difference in insulin-mediated metabolic clearance rate (MCR/I) of glucose between the oral and intravenous routes of glucose administration. Secondary endpoints were differences in insulin effect on proteolysis, ketogenesis, lipolysis and glucagon levels. In this parallel cohort study, we administered multiple oral glucose loads to 23 participants (aged between 18 and 65 years) with morbid obesity and with normal or impaired glucose tolerance or type 2 diabetes. In a different session, we administered isoglycaemic intravenous glucose infusions (IGIVI) to match the plasma glucose levels observed during the oral challenges. Glucose rate of appearance (Ra) and disappearance (Rd) and endogenous glucose production (EGP) were calculated by infusing [6,6-2H2]glucose with or without oral [U-13C6]glucose. Plasma small polar metabolites were measured by gas chromatography and time-of-flight mass spectrometry. Lipids were measured by ultra-HPLC and quadrupole mass spectrometry. Glucagon-like peptide-1, insulin, C-peptide and glucagon were also measured. Participants, caregivers, people doing measurements or examinations, and people assessing the outcomes were unblinded to group assignment. Glucose MCR/I was significantly higher during IGIVI than during oral glucose administration, independently of glycaemic status (12 ± 6 for IGIVI vs 7.4 ± 3 ml min−1 kg−1 per nmol/l for oral, p< 0.001 from paired t test). Insulin secretion was higher during oral administration than during IGIVI (p< 0.001). The disposition index was significantly lower during the oral procedure: 4260 ± 1820 vs 5000 ± 2360 (ml min−1 kg−1 (nmol/l)−1 pmol/min; p = 0.005). Insulin clearance was significantly higher when glucose was infused rather than ingested (2.53 ± 0.82 vs 2.16 ± 0.49 l/min in intravenous and oral procedure, respectively, p = 0.006). The efficacy of insulin in inhibiting lipolysis and proteolysis was decreased after oral glucose loads. A heat map diagram showed a different pattern for the metabolites between the two routes of glucose administration. Our study shows that insulin sensitivity depends on the route of glucose administration, the oral route leading to increased insulin secretion and compensatory insulin resistance compared with the intravenous route. The efficacy of insulin in blocking lipolysis and protein breakdown is lower after oral glucose loads vs the intravenous route. Our findings suggest that, while the glucose-mediated incretin release is followed by an increase in insulin release, the effect of the released insulin is limited by an increase in insulin resistance. ClinicalTrials.gov NCT03223129.

Semiglobal Sampled-Data Dynamic Output Feedback Controller for the Glucose–Insulin System

Abstract: In this paper, we deal with the problem of tracking a desired plasma glucose concentration by means of intravenous insulin administration, for Type 2 diabetic patients. A nonlinear time-delay model is used to describe the glucose–insulin regulatory system, according to which a model-based approach is exploited to design a semiglobal sampled-data dynamic output feedback controller. It is shown that emulation, by Euler approximation, of a proposed continuous-time control law yields stabilization in the sample-and-hold sense of the glucose–insulin system. The glucose regulator makes use of only sampled glucose measurements. Theoretical results are preclinically validated through a virtual environment broadly accepted as a substitute to animal trials for the preclinical testing of control strategies in plasma glucose regulation. Numerical results are encouraging and pave the way to further clinical verifications.

A revised Sorensen model: Simulating glycemic and insulinemic response to oral and intra-venous glucose load.

Abstract: In 1978, Thomas J. Sorensen defended a thesis in chemical engineering at the University of California, Berkeley, where he proposed an extensive model of glucose-insulin control, model which was thereafter widely employed for virtual patient simulation. The original model, and even more so its subsequent implementations by other Authors, presented however a few imprecisions in reporting the correct model equations and parameter values. The goal of the present work is to revise the original Sorensen's model, to clearly summarize its defining equations, to supplement it with a missing gastrio-intestinal glucose absorption and to make an implementation of the revised model available on-line to the scientific community.

HR3DHG version 1: modeling the spatiotemporal dynamics of mercury in the Augusta Bay (southern Italy)

Abstract: . The biogeochemical dynamics of Hg , and specifically of its three species Hg0 , HgII , and MeHg (elemental, inorganic, and organic, respectively), in the marine coastal area of Augusta Bay (southern Italy) have been explored by the high-resolution 3D Hg (HR3DHG) model, namely an advection–diffusion–reaction model for dissolved mercury in the seawater compartment coupled with a diffusion–reaction model for dissolved mercury in the pore water of sediments in which the desorption process for the sediment total mercury is taken into account. The spatiotemporal variability of the mercury concentration in both seawater ( [HgD] ) and the first layers of bottom sediments ( [ Hg D sed ] and [ Hg T sed ] ), as well as the Hg fluxes at the boundaries of the 3D model domain, have been theoretically reproduced, showing acceptable agreement with the experimental data collected in multiple field observations during six different oceanographic cruises. Also, the spatiotemporal dynamics of the total mercury concentration in seawater have been obtained by using both model results and field observations. The mass balance of the total Hg species in seawater has been calculated for the Augusta Harbour, improving previous estimations. The HR3DHG model could be used as an effective tool to predict the spatiotemporal distributions of dissolved and total mercury concentrations, while contributing to better assessing hazards for the environment and therefore for human health in highly polluted areas.

Comparison between two different cardiovascular models during a hemorrhagic shock scenario.

Abstract: Hemorrhagic shock is a form of hypovolemic shock determined by rapid and large loss of intravascular blood volume and represents the first cause of death in the world, whether on the battlefield or in civilian traumatology. For this, the ability to prevent hemorrhagic shock remains one of the greatest challenges in the medical and engineering fields. The use of mathematical models of the cardiocirculatory system has improved the capacity, on one hand, to predict the risk of hemorrhagic shock and, on the other, to determine efficient treatment strategies. In this paper, a comparison between two mathematical models that simulate several hemorrhagic scenarios is presented. The models considered are the Guyton and the Zenker model. In the vast panorama of existing cardiovascular mathematical models, we decided to compare these two models because they seem to be at the extremes as regards the complexity and the detail of information that they analyze. The Guyton model is a complex and highly structured model that represents a milestone in the study of the cardiovascular system; the Zenker model is a more recent one, developed in 2007, that is relatively simple and easy to implement. The comparison between the two models offers new prospects for the improvement of mathematical models of the cardiovascular system that may prove more effective in the study of hemorrhagic shock.

A Simple Cardiovascular Model for the Study of Hemorrhagic Shock.

Abstract: Hemorrhagic shock is the number one cause of death on the battlefield and in civilian trauma as well. Mathematical modeling has been applied in this context for decades; however, the formulation of a satisfactory model that is both practical and effective has yet to be achieved. This paper introduces an upgraded version of the 2007 Zenker model for hemorrhagic shock termed the ZenCur model that allows for a better description of the time course of relevant observations. Our study provides a simple but realistic mathematical description of cardiovascular dynamics that may be useful in the assessment and prognosis of hemorrhagic shock. This model is capable of replicating the changes in mean arterial pressure, heart rate, and cardiac output after the onset of bleeding (as observed in four experimental laboratory animals) and achieves a reasonable compromise between an overly detailed depiction of relevant mechanisms, on the one hand, and model simplicity, on the other. The former would require considerable simulations and entail burdensome interpretations. From a clinical standpoint, the goals of the new model are to predict survival and optimize the timing of therapy, in both civilian and military scenarios.

Decision support for medical disasters: Evaluation of the IMPRESS system in the live Palermo demo

Abstract: Background In medical disasters, coordination, information flows, and decision making are crucial for response and management Different factors contribute to thwart the response efforts Some are due to the coordination of the many agencies active in disaster response Support tools for gathering and analysing data may support task assignment, resource allocation, and acquisition as well as training at different decision levels (in the field and in command-rooms) Validation of Decision Support Systems (DSS) in simulated contexts, simulating real situations, becomes mandatory In the framework of testing and validation of the IMPRESS project (and of its INCIMOB and INCIMAG tools), one scenario was planned in Palermo, a city of 700,000 inhabitants in the Mediterranean Area of Southern Italy, simulating the sudden liberation of high concentrations of toxic compounds from a fire in Palermo harbor Emergency Agencies, a real and a simulated Hospital and operators in the field used the system during the response phase A group of 20 external Observers participated for evaluation purposes During a joint debriefing session, ad-hoc questionnaires were administered IMPRESS was useful in improving the execution of important functions during the DEMO; Users agreed about the advantages of the use of IMPRESS tools for conducting crisis activities INCIMOB use resulted more problematic from an operational point of view Shortcomings were detected and criticisms were raised due mainly to the lack of training and direct voice communication Evaluation of DSS in Emergency medicine can benefit from live exercises to highlight weaknesses in both the response system and decision support